Mouse epidermal cell cultures and epidermal cell lines are utilized as models for studying mechanisms of epithelial carcinogenesis in vitro. Epidermal cells differentiate to produce normal keratin and retain epidermal-specific cell surface antigens in vitro yielding excellent markers for differentiation. Tumor promoters alter epidermal cell differentiation and induce certain cell strains to gain the ability to grow in agar. Tumor promoters also induce new synthesis of ornithine decarboxylase as well as prolong the half-life of the activity of this enzyme. Active metabolites of benzo(a)pyrene induce gaps in replicating strands of DNA; the ratio of gaps to bound BP molecules is one for the most carcinogenic metabolite and two for a less carcinogenic stereoisomer suggesting a difference in repair processes for each metabolite. Radioimmunoassay detection of carcinogen-DNA adducts is both highly specific and sensitive and can follow binding and removal of a specific DNA product as well as molecular alteration of the bound carcinogen.